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Biomedical subjects

M Gebhardt

Publications and source records attributed to M Gebhardt.

At least 19 recordsLinked to original sources

Physiological characterisation of antennal mechanosensory descending interneurons in an insect (Gryllus bimaculatus, Gryllus campestris) brain.

We investigated five different descending brain interneurons with dendritic arborizations in the deutocerebrum in the crickets Gryllus bimaculatus and G. campestris. These interneurones convey specific antennal mechanosensory information to the ventral nerve cord and all responded to forced antennal movements. These interneurones coded for velocity and showed preferences for distinct sectors of the total range of antennal movements. Their axons descended into the posterior connective either ipsilateral or contralateral to the cell body. Electrical stimulation of sensory nerves indicated that the interneurons received input from different afferents of the two antennal base segments. One interneuron had a particularly large axon with a conduction velocity of 4.4 ms(-1). This was the only one of the five interneurons that also received visual input. Its activity was reduced during voluntary antennal movements. The reduction in activity occurred even after de-efferentation of the antenna, indicating that it had a central origin. Although we do not have experimental evidence for behavioural roles for the descending antennal mechanosensory interneurons, the properties described here suggest an involvement in the perception of objects in the path of the cricket.

Animals↗

[A severe epicutaneous test reaction to the bufexamac in a hemorrhoidal therapeutic preparation].

HISTORY AND FINDINGS: A 49-year-old woman presented with acute perianal vesicular/bullous contact dermatitis. Other areas were over the trunk, face, neck and wrists. She reported occasional application of an ointment (Mastu S) to treat her hemorrhoids. INVESTIGATION: Patch tests (basic series, anal block, own ointment, local anesthetic, cosmetics) provoked strong vesicular and bullous reactions of persisting crescendo type, spreading far beyond the site of application, to Bufexamac, to a derivative of hydroxxamine acid, and to local applied ointment with mild or moderate antiinflammatory action. TREATMENT AND COURSE: A week after the patch tests there was a flare-up of the previous foci of dermatitis. These reactions subsided two days later after intravenous injection of prednisolone. The skin lesions healed after rapid reduction of the systemic treatment and local application of corticosteroids, bathing with tanning substances and basic preparations. CONCLUSION: While Bufexamac is not absorbed when applied rectally, perianal contamination may not be avoidable on intra-anal application and can produce sensitization.

Acute Disease↗

High frequency of non-B subtypes in newly diagnosed HIV-1 infections in Switzerland.

HIV-1 subtypes were determined in newly diagnosed residents of Switzerland. Blood was anonymously collected from patients with a first confirmed positive HIV-1 test result. Viral DNA from the env V3-V5 region was amplified by nested polymerase chain reaction (PCR) and screened for subtype B by heteroduplex mobility assay. All amplicons not identified as B were sequenced. From November 1996 to February 1998, 206 samples were analyzed. Main transmission risks were unprotected heterosexual (55.7%) or homosexual (27.1%) sexual contact or intravenous drug use (12.9%). Subtype B dominated in patients of Swiss, other European, American, or Asian citizenship; particularly high frequencies were found in homosexuals (97%) and drug users (94%). Non-B subtypes including A, C, D, E, F, G, H, a possible B/F recombinant, and a sequence related to J were present in 28.2% (95% confidence interval [CI], 22.9%-35.0%). Non-B were frequent in African citizens (95%), heterosexually infected individuals (44%), and women (43%). Heterosexually infected Swiss males harbored non-B strains in 18% and females in 33%. The results document a change in the epidemiology of newly diagnosed HIV-1 infections in Switzerland: predominance of heterosexual transmission and a high frequency of non-B subtypes.

Adult↗

Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study.

BACKGROUND: AIDS reporting in Switzerland is mandatory by law. For the first time since the beginning of the epidemic, health authorities observed a decline in AIDS surveillance reports, from 545 new cases in 1995 to 459 in 1996, a decrease of 86 cases. OBJECTIVE: To examine the extent to which this decline in AIDS surveillance reports is attributable to the introduction of antiretroviral combination therapy. PATIENTS AND SETTING: Swiss HIV Cohort Study, a multicentre cohort of adult HIV-infected patients with national coverage. Participants at risk of developing a first AIDS-defining event, defined as persons with a CD4 cell count below 200 x 10(6)/l or in clinical stage B, were studied. METHODS: A parametric statistical survival model was used to estimate the number of AIDS cases expected in the absence of combination therapies. Taking reporting delays into account, the effect of the introduction of combination therapies in the cohort on national AIDS reports was estimated from the difference between the number of expected and observed cases. RESULTS: A total of 4915 participants contributed 10755 person-years and 2366 initial AIDS events. Between 1990 and 1994, about 35% received antiretroviral therapy, predominantly monotherapy. In 1995 and 1996, the prevalence of antiretroviral therapy increased steadily due to the introduction of dual and triple combinations. The mid-year prevalence of use of combination therapies was 6% in 1994, 13% in 1995, and 48% in 1996. The difference between expected and observed cases per half-year increased from 12 in the first 6 months of 1994 to 69 in the second half of 1996. Taking reporting delays into account, we estimated that 43 (95% confidence interval, 17-69) of the deficit of 86 reports could be attributed to combination therapies. CONCLUSION: The introduction of antiretroviral combination therapies in a single cohort study explained 50% of the decline in national AIDS surveillance reports. Monitoring the use and effectiveness of antiretroviral therapy must become an important component of AIDS surveillance systems.

Acquired Immunodeficiency Syndrome↗

Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients with contact allergy.

We investigated whether patients with contact allergy differed from non-contact-allergic, non-atopic controls with regard to genotype and phenotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). 55 contact-allergic patients recruited from the Information Network of Departments of Dermatology (IVDK) were compared to 85 controls from among local health care personnel. NAT2 activity was calculated from HPLC analysis of the ratio of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX) in the urine. NAT2 genotype was determined by polymerase chain reaction (PCR). A statistically significantly increased proportion of rapid acetylators was found in contact-allergic patients. This may have 2 possible implications: acetylation may enhance contact sensitization; or NAT2 status may be a genetic marker for contact sensitizability.

Acetylation↗

Development of occupational skin diseases during vocational training in baker and confectioner apprentices: a follow-up study.

Baker and confectioner apprentices have been included in a prospective follow-up study in the region of East Thuringia, to evaluate risk factors for the development of hand dermatitis. Starting in August 1996, the apprentices have been interviewed and examined in a standardized way right at the beginning (n=91) of their vocational training, 6 (n=79) and 12 months (n=63) later. To gain objective data, TEWL score was also assessed at 3 standardized sites on the hands. In their case histories, 3.3% (n=3) of the apprentices reported hand dermatitis. The 1st assessment after 2 to 4 weeks vocational training revealed hand eczema in 17.5% (n=16) of the individuals. At the follow-up after 6 months of training 29.1% (n=23), and after 12 month of training 27.0% (n=17), of the apprentices had hand dermatitis of mild to moderate severity. Within 6 months, the TEWL score rose significantly (p<0.001) from 11.9 g m(-2) h(-1) (-/+5.4) to 16.8 g m(-2) h(-1) (-/+9.5). After 12 months, the TEWL score was 14.9 g m(-2) h(-1) (-/+4.6). For the atopic skin diathesis (>10 points of Diepgen's atopy score), there was a significant tendency to be a predictive factor for the development of occupational hand dermatitis. TEWL score failed to correlate with the development of skin damage in our study. The same was true for respiratory atopy and metal sensitization.

Adolescent↗

A new mutation in the type II hair cortex keratin hHb1 involved in the inherited hair disorder monilethrix.

Monilethrix is a rare dominant hair disease characterized by beaded or moniliform hair which results from the periodic thinning of the hair shaft and shows a high propensity to excess weathering and fracturing. Several cases of monilethrix have been linked to the type II keratin gene cluster on chromosome 12q13 and causative heterozygous mutations of a highly conserved glutamic acid residue (Glu 410 Lys and Glu 410 Asp) in the helix termination motif of the type II hair keratin hHb6 have recently been identified in monilethrix patients of two unrelated families. In the present study, we have investigated two further unrelated monilethrix families as well as a single case. Affected members of one family and the single patient exhibited the prevalent hHb6 Glu 410 Lys mutation. In the second family, we identified in affected individuals a lysine substitution of the corresponding glutamic acid residue, Glu 403, in the type II hair keratin hHb1, suggesting that this site represents a mutational hotspot in these highly related type II hair keratins. Both hHb1 and hHb6 are largely coexpressed in cortical trichocytes of the hair shaft. This indicates that monilethrix is a disease of the hair cortex.

Amino Acid Sequence↗

Monitoring of serologic immune parameters in inflammatory skin diseases.

This paper deals with the correlation of clinical scoring and serologic markers of inflammation in atopic dermatitis and psoriasis. Serum eosinophil cationic protein (ECP), soluble interleukin-2 receptor (sIL-2R), total serum IgE, IgG and IgM anti-IgE antibodies, and IgE immune complexes were evaluated in monitoring inflammatory skin diseases such as atopic dermatitis and psoriasis. Well-established clinical activity scores were used as standards in recording skin improvement under treatment in a clinical setting. Serum ECP was found to be increased in both atopic dermatitis and psoriasis patients compared to normal controls; sIL-2R and IgE immune complexes were increased only in atopics with increased serum IgE. Anti-IgE antibodies did not show any deviation in both groups of patients. There was a significant elevation of sIL-2R and IgE immune complexes and a nonsignificant elevation of ECP in high-IgE atopics in comparison to those with normal serum IgE. In both groups of patients, there was a significant reduction of ECP and sIL-2R accompanying the improving skin condition. Serum IgE and the other immune parameters failed to respond. In contrast to other studies, serum ECP failed to correspond significantly with disease activity in our study. Our results showed measurable changes of ECP and sIL-2R for atopic dermatitis and/or psoriasis under treatment, but comparison to clinical scores remains difficult due to the different basis of the two systems. The only significant correlation was established for relative changes in sIL-2R and psoriasis area and intensity (PASI), a correlation which might be a useful approach in psoriasis.

Adolescent↗

Allergy testing in serious cutaneous drug reactions--harmful or beneficial?

We report on 3 cases of adverse cutaneous drug reactions of erythema multiforme type. Despite the serious previous clinical conditions, patch tests with the possible causative drugs have been performed in all our patients, because of multiple candidate drugs and the need of the patients for further treatment with at least some of the agents. We demonstrate that patch tests are a good and safe approach to initial evaluation of the nature of a cutaneous drug reaction. In the case of a positive patch test reaction to one of the substances, re-exposure to the non-reactants in a clinical setting is recommended. If a one-side-blinded placebo-controlled challenge test is well tolerated, then the clinician should be able to reintroduce drugs previously suspected as causing the allergy.

Adult↗

The surgical treatment of patients with osteosarcoma who sustain a pathologic fracture.

The presence of pathologic fracture in osteosarcoma raises concerns of tumor dissemination by the fracture hematoma and has been considered a contraindication to limb salvage surgery. Because this is a theoretical concern, there are little clinical data available in the literature on which to base treatment of these patients. Eighteen patients with osteosarcoma who sustained a pathologic fracture and had a minimum of 24 months of followup were reviewed retrospectively. Surgical treatment included nonoperative therapy, amputation, and limb salvage groups. Patients who refused surgical intervention (2) had a uniformly poor outcome. Patients who underwent amputation (6) had no local recurrences and 33% developed metastases. Patients who underwent limb salvage (10) experienced 3 local recurrences and 6 distant recurrences. Although the distant recurrence rate for patients undergoing amputation was no different from the rate for those undergoing limb salvage, the difference in local tumor control approached statistical significance. All patients who developed local recurrence died. Surgical treatment needs to be individualized and based on factors such as fracture displacement, stability, radiographic and histologic response to chemotherapy, and the perceived ability to resect the fracture hematoma completely.

Adolescent↗

[Effects of the 1987 revision of the definition for an AIDS case in Switzerland].

AIDS cases diagnosed in Switzerland after the revision of 1987 and reported to the Swiss Federal Office of Public Health until 31.12.1992 were categorised according to whether they conformed to the diagnostic criteria valid before the revision (= "pre-87"-group) or only to the new criteria introduced with the revision (= "post-87"-group). Compared to the "pre-87"-group, the proportion of injecting drug users was higher, the proportion of homosexual men was lower, the patients were younger and Pneumocystis carinii pneumonia (PCP) and Kaposi-sarcoma were diagnosed less frequently in the "post-87"-group. The revision of the AIDS case-definition affected the proportion of Aids-diagnoses with PCP over time. It improved the surveillance of AIDS morbidity in Switzerland but its effects must be distinguished from true phenomena of the AIDS-epidemic.

Acquired Immunodeficiency Syndrome↗

Different growth factor requirements for human Th2 cells may reflect in vivo induced anergy.

We previously reported the isolation of allergen-specific Th2 lines and clones from atopy patch test (APT) sites of atopic dermatitis (AD) patients. Upon stimulation with allergen or anti-CD3+ phorbol myristate acetate (PMA) IL-4 was released with or without IL-5, while no (or extremely low concentrations of) IL-2 and interferon-gamma (IFN-gamma) were detectable. A high IL-4/IFN-gamma ratio facilitates production of allergen-specific IgE, of which high levels are observed in AD patients. Here we show that the above mentioned Th2 cells are notably different from murine Th2 cells. Not IL-4, which is the autocrine acting growth factor for murine Th2 cells, but IL-2 was needed for proliferation of these human APT-derived Th2 lines and clones. Of significance, unless exogenous IL-2 was added, no proliferative response to allergen, presented by Epstein-Barr virus-transformed B (EBV-B) cells, non-T cells or IgE-bearing Langerhans cells (LC), occurred. Lack of proliferation and IL-2 production after full T cell receptor (TCR) triggering is a characteristic first described for in vitro anergized T cells. However, like the clones we describe in this study, anergic T cells may retain production of cytokines other than IL-2. A further resemblance between anergic T cells and the human Th2 clones reported here is that IL-4 can enhance IL-2-driven proliferation, but is not capable of inducing T cell growth by itself. The absence of IL-4-driven proliferation differentiates human Th2 cells from murine Th2 cells. Both produce IL-4 when stimulated in a cognate fashion, but only murine Th2 cells will proliferate. We conclude that the presently reported human Th2 cells are different from murine Th2 cells, in that they need other T cells to produce IL-2 required for their expansion. Moreover, the Th2 cells phenotypically resemble anergic T cells. As yet, however, we have no clue as to whether these features account for the current Th2 cells only or for human Th2 cells in general. We hypothesize that the Th2 phenotype of AD skin-derived, allergen-specific T cells may be induced in vivo by LC, which lack CD80, and therefore do not provide secondary signals through CD28-CD80 interaction.

Adult↗